Tardive dyskinesia remains a major public health problem in psychiatry. Despite increasing attention and research no safe and effective treatment has been established, therefore, identification of risk factors and prevention remain important goals. Knowledge with regard to risk factors is almost entirely based on cross-sectional prevalence surveys and retrospective data collection on important diagnostic, illness history and treatment history characteristics. The continuation of the present investigation would provide a unique opportunity to build upon a prospectively collected data base on the incidence and course of TD as well as risk factors. To date 878 patients have entered the study including 70 patients with no exposure to neuroleptics, 218 patients with less than 3 months total exposure at the time of study entry and 107 patients receiving different controlled dosage ranges of fluphenazine decanoate. The median length of total previous neuroleptic exposure at study entry (for those who have been treated) is 12 months, therefore patients are being followed from the early part of their treatment course. Sixty-four patients with a documented history of severe Parkinsonian side effects to neuroleptic treatment are also being followed. Patients are evaluated every three months with the Simpson Dyskinesia Scale, the Simpson-Angus Scale and the BPRS. Patients with questionable signs are seen monthly. Those developing presumptive TD are evaluated neuromedically, videotaped and seen every two weeks with discontinuation of neuroleptic medication whenever possible. To date 112 cases of presumptive TD have developed and a major focus of the project at present is to study TD outcome and to evaluate the effect of prospectively assessed variables on both the development of TD and its subsequent course. An additional three years will allow us to determine incidence beyond 5-6 years of cumulative neuroleptic exposure, to further characterize the long-term course of TD and to initiate major analyses of the very large data base we have accumulated.